TY - JOUR
T1 - Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis
AU - Mitsumoto, Hiroshi
AU - Garofalo, Diana C.
AU - Santella, Regina M.
AU - Sorenson, Eric J.
AU - Oskarsson, Björn
AU - Fernandes, J. americo M.
AU - Andrews, Howard
AU - Hupf, Jonathan
AU - Gilmore, Madison
AU - Heitzman, Daragh
AU - Bedlack, Richard S.
AU - Katz, Jonathan S.
AU - Barohn, Richard J.
AU - Kasarskis, Edward J.
AU - lomen-Hoerth, Catherine
AU - Mozaffar, Tahseen
AU - Nations, Sharon P.
AU - Swenson, Andrea J.
AU - Factor-Litvak, Pam
N1 - Publisher Copyright:
© 2020, © 2020 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases.
PY - 2020/4/2
Y1 - 2020/4/2
N2 - Objective: To determine the associations between plasma creatinine (PCr), plasma uric acid (PUA), and urinary oxidative stress (OS) biomarkers with the ALSFRS-R at baseline and survival in a large epidemiological cohort study (ALS COSMOS) with a well-phenotyped patient population (N = 355). Methods: Fasting plasma and first void urine samples were obtained. PCr, PUA, urinary 8-oxo-deoxy guanosine (8-oxodG), and 15-F2t-isoprostane (IsoP) were analyzed at baseline, near the midpoint of follow-up, and at the final blood draw (before death or withdrawal from study). We estimated associations between these biomarkers and the ALSFRS-R at baseline and survival. Results: At baseline, PCr correlated with ALSFRS-R (Spearman r = 0.30), percent (%) FVC (r = 0.20), PUA (r = 0.37), and 8-oxodG (r = −0.13, all p < 0.05). Baseline PCr significantly predicted survival (adjusted hazard ratio 0.28, p < 0.001). Time to death from baseline was shortest for those in the lowest two PCr quartiles relative to the highest two quartiles. PCr and ALSFRS-R values were significantly correlated at all three time points (baseline: r = 0.29, midpoint: r = 0.23, final: r = 0.38, all p < 0.001). PCr and PUA significantly declined over time, whereas OS biomarkers significantly increased over time. Conclusions: To date, PCr predicted survival the best, compared to PUA, 8-oxodG, and IsoP. Although PCr represents the degree of muscle mass, it may also represent complex biochemical changes in ALS. Because the field has no reliable prognostic biomarkers, the importance of PCr warrants further investigation through clinical studies in ALS.
AB - Objective: To determine the associations between plasma creatinine (PCr), plasma uric acid (PUA), and urinary oxidative stress (OS) biomarkers with the ALSFRS-R at baseline and survival in a large epidemiological cohort study (ALS COSMOS) with a well-phenotyped patient population (N = 355). Methods: Fasting plasma and first void urine samples were obtained. PCr, PUA, urinary 8-oxo-deoxy guanosine (8-oxodG), and 15-F2t-isoprostane (IsoP) were analyzed at baseline, near the midpoint of follow-up, and at the final blood draw (before death or withdrawal from study). We estimated associations between these biomarkers and the ALSFRS-R at baseline and survival. Results: At baseline, PCr correlated with ALSFRS-R (Spearman r = 0.30), percent (%) FVC (r = 0.20), PUA (r = 0.37), and 8-oxodG (r = −0.13, all p < 0.05). Baseline PCr significantly predicted survival (adjusted hazard ratio 0.28, p < 0.001). Time to death from baseline was shortest for those in the lowest two PCr quartiles relative to the highest two quartiles. PCr and ALSFRS-R values were significantly correlated at all three time points (baseline: r = 0.29, midpoint: r = 0.23, final: r = 0.38, all p < 0.001). PCr and PUA significantly declined over time, whereas OS biomarkers significantly increased over time. Conclusions: To date, PCr predicted survival the best, compared to PUA, 8-oxodG, and IsoP. Although PCr represents the degree of muscle mass, it may also represent complex biochemical changes in ALS. Because the field has no reliable prognostic biomarkers, the importance of PCr warrants further investigation through clinical studies in ALS.
KW - Amyotrophic lateral sclerosis
KW - biomarker
KW - creatinine
KW - oxidative stress
KW - uric acid
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U2 - 10.1080/21678421.2020.1746810
DO - 10.1080/21678421.2020.1746810
M3 - Article
C2 - 32276554
AN - SCOPUS:85083525839
SN - 2167-8421
VL - 21
SP - 263
EP - 272
JO - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
JF - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
IS - 3-4
ER -